Switch in Selectivity for Formal Hydroalkylation of 1,3-Dienes and Enynes with Simple Hydrazones

Controlling reaction selectivity is a permanent pursuit for chemists. Regioselective catalysis, which exploits and/or overcomes innate steric and electronic bias to deliver diverse regio-enriched products from the same starting materials, represents a powerful tool for divergent synthesis. Recently, the 1,2-Markovnikov hydroalkylation of 1,3-dienes with simple hydrazones was reported to generate branched allylic compounds when a nickel catalyst was used. As part of the effort, shown here is that a complete switch of Markovnikov to anti-Markovnikov addition is obtained by changing to a ruthenium catalyst, thus providing direct and efficient access to homoallylic products exclusively. Isotopic substitution experiments indicate that no reversible hydro-metallation across the metal-π-allyl system occurred under ruthenium catalysis. Moreover, this protocol is applicable to the regiospecific hydroalkylation of the distal C=C bond of 1,3-enynes.     

Ruthenium-catalyzed intermolecular coupling reactions of arylamines with ethylene and 1,3-dienes: mechanistic insight on hydroamination vs ortho-C-H bond activation

[reaction: see text]. The cationic ruthenium complex [(PCy3)2(CO)(Cl)Ru=CHCH=C(CH3)2]+BF4- was found to be an effective catalyst for the coupling reaction of aniline and ethylene to form a approximately 1:1 ratio of N-ethylaniline and 2-methylquinoline products. The analogous reaction with 1,3-dienes resulted in the preferential formation of Markovnikov addition products. The normal isotope effect of k(NH)/k(ND) = 2.2 (aniline and aniline-d7 at 80 degrees C) and the Hammett rho = -0.43 (correlation of para-substituted p-X-C6H4NH2) suggest an N-H bond activation rate-limiting step for the catalytic reaction.     

meta‐C−H Bromination on Purine Bases by Heterogeneous Ruthenium Catalysis

Methods for positionally selective remote C−H functionalizations are in high demand. Herein, we disclose the first heterogeneous ruthenium catalyst for meta ‐selective C−H functionalizations, which enabled remote halogenations with excellent site selectivity and ample scope. The versatile heterogeneous Ru@SiO₂ catalyst was broadly applicable and could be easily recovered and reused, which set the stage for the direct fluorescent labeling of purines. In contrast to palladium, rhodium, iridium, or cobalt complexes, solely the ruthenium catalysis manifold provided access to meta ‐halogenated purine derivatives, illustrating the unique power of ruthenium C−H activation catalysis.     

Regioselective Hydroalkylation and Arylalkylation of Alkynes by Photoredox/Nickel Dual Catalysis: Application and Mechanism

Alkynes are an important class of organic molecules due to their utility as versatile building blocks in synthesis. Although efforts have been devoted to the difunctionalization of alkynes, general and practical strategies for the direct hydroalkylation and alkylarylation of terminal alkynes under mild reaction conditions are less explored. Herein, we report a photoredox/nickel dual‐catalyzed anti‐Markovnikov‐type hydroalkylation of terminal alkynes as well as a one‐pot arylalkylation of alkynes with alkyl carboxylic acids and aryl bromides via a three‐component cross‐coupling. The results indicate that the transformations proceed via a new mechanism involving a single‐electron transfer with subsequent energy‐transfer activation pathways. Moreover, steady‐state and time‐resolved fluorescence‐spectroscopy measurements, density functional theory (DFT) calculations, and wavefunction analysis have been performed to give an insight into the catalytic cycle.     

Copper‐Catalyzed Regioselective Hydroalkylation of 1,3‐Dienes with Alkyl Fluorides and Grignard Reagents

Copper complexes generated in situ from CuCl₂, alkyl Grignard reagents, and 1,3‐dienes play important roles as catalytic active species for the 1,2‐hydroalkylation of 1,3‐dienes by alkyl fluorides through C? F bond cleavage. The alkyl group is introduced to an internal carbon atom of the 1,3‐diene regioselectively, thus giving rise to the branched terminal alkene product.     

Iridium‐Catalyzed Intramolecular Methoxy C−H Addition to Carbon–Carbon Triple Bonds: Direct Synthesis of 3‐Substituted Benzofurans from o‐Methoxyphenylalkynes

Catalytic hydroalkylation of an alkyne with methyl ether was accomplished. Intramolecular addition of the C?H bond of a methoxy group in 1‐methoxy‐2‐(arylethynyl)benzenes across a carbon–carbon triple bond took place efficiently either in toluene at 110 °C or in p‐xylene at 135 °C in the presence of an iridium catalyst. The initial 5‐exo cyclization products underwent double‐bond migration during the reaction to give 3‐(arylmethyl)benzofurans in high yields.     

CH Functionalization of Phenols Using Combined Ruthenium and Photoredox Catalysis: In Situ Generation of the Oxidant

A combination of ruthenium and photoredox catalysis allowed the ortho olefination of phenols. Using visible light, the direct C? H functionalization of o‐(2‐pyridyl)phenols occurred, and diverse phenol ethers were obtained in good yields. The regeneration of the ruthenium catalyst was accomplished by a photoredox‐catalyzed oxidative process.     

Exploring Bis(cyclometalated) Ruthenium(II) Complexes as Active Catalyst Precursors: Room‐Temperature Alkene–Alkyne Coupling for 1,3‐Diene Synthesis

Described is the development of a new class of bis(cyclometalated) ruthenium(II) catalyst precursors for C? C coupling reactions between alkene and alkyne substrates. The complex [(cod)Ru(3‐methallyl)₂] reacts with benzophenone imine or benzophenone in a 1:2 ratio to form bis(cyclometalated) ruthenium(II) complexes ( 1 ). The imine‐ligated complex 1 a promoted room‐temperature coupling between acrylic esters and amides with internal alkynes to form 1,3‐diene products. A proposed catalytic cycle involves C? C bond formation by oxidative cyclization, β‐hydride elimination, and C? H bond reductive elimination. This Ru^II/Ru^IV pathway is consistent with the observed catalytic reactivity of 1 a for mild tail‐to‐tail methyl acrylate dimerization and for cyclobutene formation by [2+2] norbornene/alkyne cycloaddition.     

Micellar Catalysis for Ruthenium(II)‐Catalyzed C−H Arylation: Weak‐Coordination‐Enabled C−H Activation in H2O

Chemoselective C?H arylations were accomplished through micellar catalysis by a versatile single‐component ruthenium catalyst. The strategy provided expedient access to C?H‐arylated ferrocenes with wide functional‐group tolerance and ample scope through weak chelation assistance. The sustainability of the C?H arylation was demonstrated by outstanding atom‐economy and recycling studies. Detailed computational studies provided support for a facile C?H activation through thioketone assistance.     

Solvent-free hydroalkylation of olefins with 1,3-diketones catalyzed by phosphotungstic acid

An efficient and convenient method for the direct hydroalkylation of styrene and norborene with 1,3-diketones has been developed by using 12-phosphotungstic acid as an eco-friendly, and air- and moisture-tolerable catalyst. Reactions proceeded without any solvent, providing a clean access to alkylated 1,3-diketones.     

Electrooxidative Ruthenium‐Catalyzed C−H/O−H Annulation by Weak O‐Coordination

Electrocatalysis has been identified as a powerful strategy for organometallic catalysis, and yet electrocatalytic C?H activation is restricted to strongly N‐coordinating directing groups. The first example of electrocatalytic C?H activation by weak O‐coordination is presented, in which a versatile ruthenium(II) carboxylate catalyst enables electrooxidative C?H/O?H functionalization for alkyne annulations in the absence of metal oxidants; thereby exploiting sustainable electricity as the sole oxidant. Mechanistic insights provide strong support for a facile organometallic C?H ruthenation and an effective electrochemical reoxidation of the key ruthenium(0) intermediate.     

On the Mechanism of Bifunctional Squaramide‐Catalyzed Organocatalytic Michael Addition: A Protonated Catalyst as an Oxyanion Hole

A joint experimental–theoretical study of a bifunctional squaramide‐amine‐catalyzed Michael addition reaction between 1,3‐dioxo nucleophiles and nitrostyrene has been undertaken to gain insight into the nature of bifunctional organocatalytic activation. For this highly stereoselective reaction, three previously proposed mechanistic scenarios for the critical C?C bond‐formation step were examined. Accordingly, the formation of the major stereoisomeric products is most plausible by one of the bifunctional pathways that involve electrophile activation by the protonated amine group of the catalyst. However, some of the minor product isomers are also accessible through alternative reaction routes. Structural analysis of transition states points to the structural invariance of certain fragments of the transition state, such as the protonated catalyst and the anionic fragment of approaching reactants. Our topological analysis provides deeper insight and a more general understanding of bifunctional noncovalent organocatalysis.     

Ruthenium‐Catalyzed Hydroarylation of Methylenecyclopropanes through C?H Bond Cleavage: Scope and Mechanism

Intermolecular hydroarylation reactions of highly strained methylenecyclopropanes 2‐phenylmethylenecyclopropane ( 1 ), 2,2‐diphenylmethylenecyclopropane ( 2 ), methylenespiropentane ( 3 ), bicyclopropylidene ( 4 ), (dicyclopropylmethylene)cyclopropane ( 5 ), and benzhydrylidenecyclopropane ( 6 ) through C? H bond functionalization of 2‐phenylpyridine ( 7 a ) and other arenes with directing groups were studied. The reaction was very sensitive to the substitution on the methylenecyclopropanes. Although these transformations involved (cyclopropylcarbinyl)–metal intermediates, substrates 1 and 4 furnished anti‐Markovnikov hydroarylation products with complete conservation of all cyclopropane rings in 11–93 % yield, whereas starting materials 3 and 5 were inert toward hydroarylation. Methylenecyclopropane 6 formed the products of formal hydroarylation reactions of the longest distal C? C bond in the methylenecyclopropane moiety in high yield, and hydrocarbon 2 afforded mixtures of hydroarylated products in low yields with a predominance of compounds that retained the cyclopropane unit. As byproducts, Diels–Alder cycloadducts and self‐reorganization products were obtained in several cases from substrates 1 – 3 and 5 . The structures of the most important new products have been unambiguously determined by X‐ray diffraction analyses. On the basis of the results of hydroarylation experiments with isotopically labeled 7 a ‐[D₅], a plausible mechanistic rationale and a catalytic cycle for these unusual ruthenium‐catalyzed hydroarylation reactions have been proposed. Arene‐tethered ruthenium–phosphane complex 53 , either isolated from the reaction mixture or independently prepared, did not show any catalytic activity.     

Catalyst‐Dependent Chemoselective Formal Insertion of Diazo Compounds into C−C or C−H Bonds of 1,3‐Dicarbonyl Compounds

A catalyst‐dependent chemoselective one‐carbon insertion of diazo compounds into the C?C or C?H bonds of 1,3‐dicarbonyl species is reported. In the presence of silver(I) triflate, diazo insertion into the C(=O)?C bond of the 1,3‐dicarbonyl substrate leads to a 1,4‐dicarbonyl product containing an all‐carbon α‐quaternary center. This reaction constitutes the first example of an insertion of diazo‐derived carbenoids into acyclic C?C bonds. When instead scandium(III) triflate was applied as the catalyst, the reaction pathway switched to formal C?H insertion, affording 2‐alkylated 1,3‐dicarbonyl products. Different reaction pathways are proposed to account for this powerful catalyst‐dependent chemoselectivity.     

Cobalt‐Catalyzed Alkyne Hydrosilylation and Sequential Vinylsilane Hydroboration with Markovnikov Selectivity

A pyridinebis(oxazoline) cobalt complex is a very efficient precatalyst for the hydrosilylation of terminal alkynes with Ph₂SiH₂, providing α‐vinylsilanes with high (Markovnikov) regioselectivity and broad functional‐group tolerance. The vinylsilane products can be further converted into geminal borosilanes through Markovnikov hydroboration with pinacolborane and a bis(imino)pyridine cobalt catalyst.     

Ruthenium‐Catalyzed Transfer‐Hydrogenative Cyclization of 1,6‐Diynes with Hantzsch 1,4‐Dihydropyridine as a H2 Surrogate

The transfer‐hydrogenative cyclization of 1,6‐diynes with Hantzsch 1,4‐dihydropyridine as a H₂ surrogate was performed in the presence of a cationic ruthenium catalyst of the type [Cp′Ru(MeCN)₃PF₆]. Exocyclic 1,3‐dienes or their 1,4‐hydrogenation products, cycloalkenes, were selectively obtained, depending on the substrate structure and the reaction conditions.     

Cationic ruthenium complex of the formula [RuCl(2,6-diacetylpyridine)(PPh3)2]BArF and its catalytic activity in the formation of enol esters

A new ruthenium 2,6-diacetylpyridine complex was synthesized and applied in the atom-economic synthesis of enol esters through Markovnikov-directed addition of carboxylic acids to terminal alkynes. The ruthenium complex [RuCl(dap)(PPh₃)₂]⁺BArF^? was synthesized from [RuCl₂(PPh₃)₂] and the corresponding ligand 2,6-diacetylpyridine (dap). The complex was characterized structurally. The new ruthenium complex was utilized under ambient conditions as a catalyst in the Markovnikov addition of carboxylic acids to terminal alkynes to afford the corresponding enol esters in 93% to 52% isolated yields (85?°C, 16?h reaction time, 1?mol% catalyst loading).     

The Origin of Anti‐Markovnikov Regioselectivity in Alkene Hydroamination Reactions Catalyzed by [Rh(DPEphos)]+

The development of regioselective anti‐Markovnikov alkene's hydroamination is a long‐standing goal in catalysis. The [Rh(COD)(DPEphos)]⁺ complex is the most general and regioselective group 9 catalyst for such a process. The reaction mechanism for intermolecular hydroamination of alkenes catalyzed by [Rh(DPEphos)]⁺ complex is analyzed by means of DFT calculations. Hydroamination (alkene vs. amine activation routes) as well as oxidative amination pathways are analyzed. According to the computational results the operating mechanism can be generally described by alkene coordination, amine nucleophilic addition, proton transfer through the metal center and reductive elimination steps. The mechanism for the formation of the oxidative amination side product goes via a β‐elimination after the nucleophilic addition and metal center protonation steps. The origin of the regioselectivity for the addition process (Markovnikov vs. anti‐Markovnikov additions) is shown to be not charge but orbitally driven. Remarkably, η² to η¹ slippage degree on the alkene coordination mode is directly related to the regioselective outcome.     

A Combined Experimental and Computational Study on the Cycloisomerization of 2‐Ethynylbiaryls Catalyzed by Dicationic Arene Ruthenium Complexes

Ruthenium‐catalyzed cycloisomerization of 2‐ethynylbiaryls was investigated to identify an optimal ruthenium catalyst system. A combination of [η⁶‐(p‐cymene)RuCl₂(PR₃)] and two equivalents of AgPF₆ effectively converted 2‐ethynylbiphenyls into phenanthrenes in chlorobenzene at 120 °C over 20 h. Moreover, 2‐ethynylheterobiaryls were found to be favorable substrates for this ruthenium catalysis, thus achieving the cycloisomerization of previously unused heterocyclic substrates. Moreover, several control experiments and DFT calculations of model complexes were performed to propose a plausible reaction mechanism.     

A Cobalt‐Catalyzed Alkene Hydroboration with Pinacolborane

An extremely efficient cobalt catalyst for the hydroboration of both vinylarenes and aliphatic α‐olefins with pinacolborane is described, providing the anti‐Markovnikov products with excellent regio‐ and chemoselectivity, broad functional‐group tolerance, and high turnover numbers (up to 19 800). The alkene hydroboration route is further extended to a two‐step, one‐pot hydroboration and cross‐coupling of alkylboronates with aryl chlorides.